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4 January 2017 - Case of the Week #412

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Case of the Week #412

Clinical history:
A 68 year old man with ulcerative colitis and chronic rhinitis had a nasal biopsy for nasal airway obstruction and septal perforation.

Micro images:

H&E (left: low power; middle / right: high power)

What is your diagnosis?

Extranodal NK/T cell lymphoma, nasal type


Special stains:

CD3 (left: low power; right: high power)


CD56 (high power)


Test question (answer at end):

Which marker is most characteristic for NK / T cell lymphoma?


B. membranous CD3

C. CD8

D. CD16


Mature natural killer (NK) cell neoplasms are classified by the World Health Organization into NK/T cell lymphoma, nasal type, aggressive NK-cell leukemia and provisionally, chronic lymphoproliferative disorders of NK cells (see also Blood 2016 127:2375). NK/T cell lymphoma, nasal type is a predominantly extranodal lymphoma characterized by vascular damage and destruction, prominent necrosis and association with EBV. It is designated NK/T cell because while most cases appear to be genuine NK cell neoplasms, some have a cytotoxic T cell phenotype. This rare tumor is more prevalent in Asians and native American populations of Mexico, Central America and South America, males more commonly than females (Am J Surg Pathol 2000;24:1511, free full text). These tumors are almost always extranodal, most commonly in the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, palate). Extranasal NK/T cell lymphomas are similar, but arise in the GI tract, skin, testis and soft tissue. Nodal involvement occasionally occurs in secondary cases, but only rarely as the primary tumor. Marrow involvement is uncommon.

NK/T cell lymphomas are strongly associated with EBV, and EBV DNA titer is useful to monitor disease activity. These tumors also occur post-transplant or with other immunosuppressive states. Clinically, they often present with destructive sinonasal or midline facial tumors which may disseminate rapidly (prior terminology for these tumors included malignant midline reticulosis and lethal midline granuloma). They may be associated with hemophagocytic syndromes.

Histologically, they are angiocentric and angioinvasive with extensive coagulative necrosis and apoptosis. There also have perivascular and intravascular destructive infiltrates with fibrinoid changes of blood vessels even without invasion. The tumor cells are atypical small and large lymphoid cells with abundant pale or clear cytoplasm, irregular nuclear borders and immunoblasts. IHC shows positivity for CD2, CD3 (cytoplasmic CD3 epsilon, not membranous, in 56%), CD45+, CD56 (67-100%), TIA1, granzyme, EBER (96%). The T cell receptor genes are in a germ line configuration. Complex chromosomal abnormalities are frequent, and loss of chromosomes 6q, 11q, 13q and 17p are recurrent aberrations (Orphanet J Rare Dis 2013 Jul 1;8:95, Diagn Pathol 2011;6:79). The diagnosis should be questioned if negative for EBV by IHC and ISH.

Other angiocentric diseases of the head and neck include angiocentric eosinophilic fibrosis, granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, chronic cocaine usage, Erdheim Chester disease and lymphomatoid granulomatosis (Head Neck Pathol 2008;2:116).

Historically, the survival was only 30 - 40% but it has improved with more intensive therapy including upfront radiation. Unfavorable prognostic features include stage III-IV, skin/bone invasion, p53 missense mutations, high LDH, large cell immunoblastoid polymorphous histology (Hum Pathol 2004;35:86), International Prognostic Index of 2 or more (Mod Pathol 2004;17:1097), high circulating EBV DNA, EBV+ cells in bone marrow and possibly CD30 positivity (BMC Cancer 2014;14:890).

Answer to test question: A

Discussion by: Nat Pernick, M.D.

Image 01 Image 02